LIVSCI-01301; No of Pages 11

Livestock Science xxx (2010) xxx–xxx

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Livestock Science
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Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs☆
C.F.M. de Lange a,⁎, J. Pluske b, J. Gong a,c, C.M. Nyachoti d
a
Department of Animal and Poultry Science, University of Guelph, Guelph, ON, Canada N1G 2W1
b
Animal Research Institute, Murdoch University, Murdoch, WA 6150, Australia
c
Guelph Food Research Center, Agriculture and Agri-Food Canada, Guelph, ON, Canada N1G 5C9
d
Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada R3T 2N2

a r t i c l e i n f o a b s t r a c t

Available online xxxx There is a wide interest in developing management and feeding strategies to stimulate gut
development and health in newly-weaned pigs, in order to improve growth performance while
Keywords: minimizing the use of antibiotics and rather expensive feed ingredients, such as milk products.
Pigs A better understanding of the mechanisms whereby antibiotics influence animal physiology, as
Gut health well as appropriate use of disease models and in vitro techniques, will lead to the development
Gut development of alternatives to in-feed antibiotic. Given the considerable advances made in the
Antibiotics understanding of intestinal nutrient utilization and metabolism, a complimentary goal in
Feed additives
nutrition might be to formulate young pig diets with the specific task of optimizing the growth,
function and health of the gut. Important aspects of gut health-promoting pig diets are:
reduced content of protein that is fermented in the pigs' gut, minimal buffering capacity,
minimal content of anti-nutritional factors, and supply of beneficial compounds such as
immunoglobulins. The optimum dietary level and type of fibre will vary with the nature of
enteric disease challenges and production objectives. These diet characteristics are influenced
by feed ingredient composition and feed processing, including feed fermentation and
application of enzymes. A large number of feed additives have been evaluated that are
aimed at (1) enhancing the pig's immune response (e.g. immunoglobulin; ω-3 fatty acids, yeast
derived ß-glucans), (2) reducing pathogen load in the pig's gut (e.g. organic and inorganic
acids, high levels of zinc oxide, essential oils, herbs and spices, some types of prebiotics,
bacteriophages, and anti-microbial peptides), (3) stimulate establishment of beneficial gut
microbes (probiotics and some types of prebiotics), and (4) stimulate digestive function (e.g.
butyric acid, gluconic acid, lactic acid, glutamine, threonine, cysteine, and nucleotides). When
manipulating gut microbiota the positive effects of gut health-promoting microbes should be
weighed against the increased energy and nutrient costs to support these microbes. In some
instances feed additives have been proven effective in vitro but not effective in vivo. The latter
applies in particular to essential oils that have strong anti-microbial activity but appear not to
be effective in controlling bacterial pathogens when fed to pigs. A combination of different
approaches may provide the most effective alternative to in-feed antibiotics.
© 2010 Elsevier B.V. All rights reserved.

1. Introduction

☆ This paper is part of the special issue entitled “11th International

Symposium on Digestive Physiology of Pigs.”
⁎ Corresponding author. Tel.: + 1 519 824 4120x56477; fax: +1 519 836
9873.
E-mail address: cdelange@uoguelph.ca (C.F.M. de Lange).
There is a wide interest in developing management and
feeding strategies to stimulate gut development and health in
young pigs. The ultimate aim of these strategies is to improve
productivity of pigs around the time of weaning, while

1871-1413/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.livsci.2010.06.117

Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
2 C.F.M. de Lange et al. / Livestock Science xxx (2010) xxx–xxx
minimizing the use of antibiotics and rather expensive feed
ingredients, such as milk products. Indeed, under practical
conditions and both shortly before and after weaning pigs
probably achieve less than 50% of their growth performance
potential (Harrell et al., 1993).
Large amounts of research have been conducted evaluat-
ing the impact of a wide range of feed ingredients and feed
additives on various aspects of gut health and development in
pigs. Moreover, extensive reviews have been written on this
topic (e.g. Simon et al., 2003; Mroz et al., 2006; Lallès et al.,
2007; Halas et al., 2007). It is beyond this contribution to
summarize the vast amount of information that has been
generated in this area of research. The focus of this paper is to
highlight key underlying concepts that allow a better
understanding of the value of selected nutrients, feed
ingredients and additives to stimulate gut health and
development. The emphasis is on a newly-weaned pig, but
concepts may be relevant to older pigs as well.
2. Experimental approaches to explore gut health and
development
The gastrointestinal tract (GIT) of a pig is a complex
environment. In particular in newborns and around the time of
weaning, the pigs' gut rapidly changes in size, has high protein
turnover rates, undergoes rapid changes in microbiota, and
quickly alters its digestive and immune functions (Pluske et al.,
1997; Vente-Spreeuwenberg and Beynen, 2003; Burrin and
Stoll, 2003; Lallès et al., 2004). These changes are influenced by
the pigs' environment, feeding strategies, age at weaning, and
pig genotype and are mediated by psychological and beha-
vioural stress. Burrin and Stoll (2003) have divided these
changes into the acute phase, observed within the first five to
seven days after weaning, and the adaptive phase, which occurs
subsequently (Fig. 1). Burrin and Stoll (2003) make the
distinction between acute and adaptive phases based primarily
on the changes in feed intake, since it takes about seven days
for weaned pigs to learn how to eat and resume a level of dry
matter intake (at least) that is comparable to that during the
pre-weaning period (Pluske et al., 1997).
Given these complexities and rapid changes after weaning
it is naïve to suggest that a limited number of feed additives
Fig. 1. Acute and adaptive phases in development of early-weaned pigs
(adapted from Burrin and Stoll, 2003).
Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
can be effective in stimulating gut development and health in
different groups of pigs that are managed under wide ranging
environmental conditions. This also supports the need to
explore underlying mechanisms when evaluating the func-
tional properties of feed ingredients and feed additives, so
that we may better understand under what conditions we can
achieve the optimal response to dietary interventions. Key
aspects of gut functionality that should be considered include
digestive capacity (activity of pancreatic and brush-border
enzymes), absorptive capacity, chemical and physical barrier,
microbiota load and diversity, and immune function. Within
this context it is remarkable how limited our understanding is
of how antibiotics interact with gut tissue, either directly or
indirectly via microbiota and fermentation products (e.g.
Niewold 2007). Such understanding is critical for finding
effective alternatives to antibiotics.
Ultimately, we wish to improve productivity of pigs
managed under commercial conditions. However, it is
generally a challenge for researchers to obtain reliable
experimental data from commercial pig units that will
allow us to explore underlying mechanisms or to evaluate a
wide range of feed additives. On the other hand, it can be a
challenge to properly represent commercial conditions in
research units. Here the use of in vitro techniques and
infectious disease models may be considered as well. For
example, Ussing chambers may be used to evaluate various
aspects of mucosal functionality–such as permeability, ab-
sorptive capacity and secretary function–allowing a rapid
screening of feed additives and feed ingredients (Boudry
et al., 2004; Montagne et al., 2007). Alternatively, the anti-
microbial properties of a wide range of feed additives may be
explored in a very simple in vitro system (Si et al., 2006a,b).
But care should be taken with the interpretation of in vitro
findings. For example, the in vitro determined anti-microbial
properties of various essential oils are diminished substan-
tially when these are determined with the presence of feed in
the in vitro system (Si et al., 2006b), probably because
essential oils are adsorbed quickly to feed particles. Observa-
tions made in vitro need to be confirmed with key measure-
ments made in vivo.
One approach to evaluating substitute products for
antibiotics in vivo is to use an appropriate disease model. In
the post-weaning period where obviously most interest lies
with the use of alternative/replacement products for anti-
microbials, numerous research groups have used a challenge
model per os of post-weaning diarrhoea (PWD) using specific
pathogenic strains of enterotoxigenic Escherichia coli (ETEC)
(e.g. Madec et al., 2000; Owusu-Asiedu et al., 2002, 2003a,b;
Montagne et al., 2004; Bhandari et al., 2008). Such models
have been used, amongst other things, to examine whether a
particular feed additive or dietary strategy is effective in
controlling PWD. Other authors (e.g, Bhandari et al., 2008)
used a disease challenge model to examine effects of feeding
different diets on microbial diversity and inflammatory
responses after weaning. A major advantage of using such
an in vivo model is that the impacts of the particular product/
diet can be assessed within the context of an infectious
pathogenic agent being part of the ecosystem of the
gastrointestinal tract. However some key concerns still exist
regarding effects of a challenge model on between-animal
variabilities, both in pathogen load and in the animal's
 C.F.M. de Lange et al. / Livestock Science xxx (2010) xxx–xxx
response to the pathogen, changes in the pig's responses to
the pathogen over time, and interactive effects between
different pathogens. A criticism often directed at disease
challenge models to induce diarrhoea after weaning is that
the incidence and severity of the diarrhoea observed is often
less than that experienced in commercial herds where dietary
anti-microbial compounds are not included (Callesen and
Hansen, personal communication; Denmark). Indeed, there is
often a fine line in using an E. coli-challenge model between
causing a mild level of diarrhoea and (unintentionally)
causing enterotoxaemia and the death of some pigs.
In the absence of an in vitro system that effectively
simulates the dynamic nature of the gastrointestinal tract,
interesting findings have arisen from using disease models.
For example, a recent study by Halas et al. (2009) tested the
hypothesis that feeding diets supplemented with inulin (8%
of the diet) and benzoic acid (0.5% of the diet) will reduce
faecal ETEC shedding and the incidence of PWD, following
oral dosing of pigs after weaning with 3 ml of broth contain-
ing 3 × 107, 2 × 109, 1 × 1010 and 5 × 108 colony-forming units
(CFU) of a freshly grown strain of ETEC serotype O149:K91:
K88 (toxins LT, STa, and STb). Dietary supplementation with
inulin, either alone or in combination with benzoic acid,
reduced the number of days of diarrhoea in pigs weaned at
21 days of age without significantly affecting average ETEC
shedding (Table 1). Benzoic acid, on the other hand, did not
affect the incidence of PWD and did not reduce average ETEC
shedding when supplemented without inulin. Some previous
studies have found no relationship between clinical signs of
diarrhoea and ETEC shedding (Madec et al., 2000; Callasen et
al., 2007; Kim et al., 2008). In the Halas et al. (2009) study,
however, a higher faecal consistency score (more wet faeces)
was associated with increased faecal ETEC shedding
(R2 = 0.394, P = 0.001). This may be a reflection of inulin,
either by itself or in the combination with benzoic acid,
reducing the number of faecal ETEC shedding days
(P = 0.041).
For on an extensive assessment of indicators of gut
functionality in young pigs the reader is referred to Montagne
Table 1
Effects of benzoic acid (BA) and inulin (IN) supplementation on the
incidence of diarrhoea, faecal consistency (FC) and ETEC shedding in ETEC-
challenged weaner pigs a.
Dietary treatment
Benzoic 0 0.5 P-value
acid, %
Inulin, % 0 8 0 8 SEM BA IN BA × IN Time
Days with 2.6 1.2 2.9 0.8 0.28 0.982 0.001 0.496
diarrhoea b
Average FC c 3.2 2.9 3.1 2.5 0.10 0.071 0.022 0.563 0.001
Days with 1.3 0.7 1.2 0.4 0.20 0.539 0.041 0.532
ETEC
shedding d
a and its relationship to post-weaning disturbances such as
Adapted from Halas et al. (2009). Values represent means and pooled
standard errors.
b
Diarrhoea represents number of days with FC ≥ 4. Diarrhoeal days
ranged from day 4 to day 9 post-weaning.
c
Least-square means and pooled standard errors from observations on
days 4, 5, 6, 7, 8 and 9 (individual observation for each pig; FC ranges from 1
to 5).
d
Mean values and pooled standard errors; ETEC shedding represents
number of days between days 4 and 7 post-weaning with ETEC ≥ 1.
Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
3
et al. (2007). In this review indicators are suggested to assess
gut functionality during the acute post-weaning phase, in
response to feed intake, and to characterize gut maturation.
The rapid development of molecular techniques will allow us
to study mechanisms at a more fundamental level based on
gene expression profiles, genetic markers, proteomics and
metabolomics.
3. Feeding the gut
A major consequence of the events that occur in the post-
weaning period is essentially a remodelling of the entire GIT,
and in this are changes in the way that the GIT functions from
a biochemical, physiological and immunological perspective.
In the past, diets for newly-weaned pigs have largely been
formulated on the basis of overcoming the limitations or
immaturity in digestive tract function (e.g., pancreatic and
brush-border enzymes) in order to maximize growth of the
whole animal, with due recognition to the cost of raw
materials and processing. Research summarised in the
excellent review by Burrin and Stoll (2003), and more
recently with reference to the amino acid arginine (e.g. Wu
et al., 2007), suggests that given the considerable advances
made in the understanding of intestinal nutrient utilization
and metabolism, an alternate or even complimentary goal in
nutrition might be to formulate young pig diets with the
specific task of optimizing the growth, function and health of
the gut. Burrin and Stoll (2003) extensively summarised the
major nutrients involved in GIT metabolism in the young pig,
and from this discussion of intestinal nutrient utilization,
suggested the most promising candidates to be glutamine,
glutamate and threonine for the formulation of a ‘gut friendly’
diet. In this regard, several essential and non-essential amino
acids are thought to play a role with regard to their metabolic,
physiological, immunological and therapeutic effects on the
GIT and on the whole organism (review by Kim et al., 2007).
Apart from their role as building blocks for peptides and
proteins, amino acids can have bioactive properties. Particu-
larly in certain disease conditions, specific amino acids can
promote health by improving (gut) tissue anabolism, by
reducing stress and by modulating immunology. These amino
acids can be supplemented to the diet in case of a relative
deficiency during disease. Indeed, experimental results
suggest that the profile of amino acids required for the
immune system differs substantially from that for growth
(Reeds et al., 1994). On top of that, surplus administration of
certain dietary amino acids has been shown to be necessary
for inducing significant bioactivity for therapeutic purposes
(Massey et al., 1998).
4. Dietary fibre in post-weaning diets
The roles of ‘dietary fibre’ in post-weaning diets for pigs
diarrhoea have been of interest to nutritionists and veter-
inarians for many years, and continues to be so. Curiously, and
unlike nutrients and dietary components (e.g. energy) where
there are firm dietary recommendations, there are no such
recommendations for ‘dietary fibre’, with the dietary level
used being a consequence of the ingredients used to make the
diet at least-cost. Partly because of this, there has been
4 C.F.M. de Lange et al. / Livestock Science xxx (2010) xxx–xxx

considerable interest in the use of ‘dietary fibre’ in amelio- Table 2

rating post-weaning GIT disturbances. Performance, large intestinal weights, VFA levels and ileal viscosity in non-
infected and infected pigs fed either a rice-based diet or one containing pearl
Reports dating back to the 1960s and 1970s showed that barley a.
the addition of insoluble fibre sources such as the husks from
cereals, e.g., barley, could reduce the excretion of haemolytic Non-infected Infected P-value
pigs pigs
E. coli and the incidence of diarrhoea after weaning. For
example, Smith and Halls (1968) found that barley hulls fed Rice b Barley c Rice Barley SEM Diet Disease
ad libitum, but not pearl barley meal, prevented disease in Carcass gain, 74 26 − 28 − 56 36.3 * ***
weaner pigs inoculated with E. coli. Those fed barley meal g/day
remained susceptible to PWC. The barley fibre used was the Large 2.7 3.8 2.6 3.2 0.62 ** NS
outer hull of barley, collected in the making of pearled barley. intestine, %
LW d
Barley hulls contain a considerable amount of insoluble non- VFA (mM), 84 114 60 78 20.4 ** **
starch polysaccharides (NSP) and lower levels of soluble NSP. distal colon
Barley meal, on the other hand, would have a higher pH, distal 6.8 6.1 6.8 6.5 0.37 ** NS
proportion of soluble NSP. Diets used in trials by Bertschinger colon
E. coli in 0 0 0.9 4.2 2.44 *
et al. (1978,1979) that were associated with reduced E. coli
jejunum e
proliferation and diarrhoea were high in crude fibre (10–17%) E. coli in 0 0 3.2 6.2 1.89 **
and low in nutrients, particularly crude protein. Moreover, colon e
Bolduan et al. (1988) and Aumaitre et al. (1995) commented Viscosity in 2.1 2.8 1.6 2.3 1.13 * *
that the ‘appropriate addition’ of insoluble fibre sources ileum, cP

might ameliorate PWD. Bolduan et al. (1988), for example,
presented evidence showing that the production of diamines
in the colon, which are implicated in PWD, reduced linearly
with an increase in the crude fibre content of a weaner feed.
Nevertheless and as evidenced by research in Australia
and Spain using cooked/uncooked rice fed to newly-weaned
pigs (eg, Hopwood et al., 2005; Vicente et al., 2008), feeding
diets lower in dietary fibre paradoxically may also have
benefits in terms of reducing PWD and (or) enhancing
growth in the post-weaning period. Using an E. coli-challenge
model, McDonald et al. (2001a,b) demonstrated that feeding
a diet based on cooked white rice and animal protein sources
reduced the number of ETEC in the small intestine and colon
commensurate with better post-weaning performance, rela-
tive to pigs fed pearl barley (Table 2). These data suggest that
the question of the correct amount of dietary fibre to include
in a weaner diet is complex, as it most likely depends on what
the nutritionist/producer is trying to achieve, and may be
better answered by investigating dietary ingredients that
deliver an appropriate combination of carbohydrates (e.g.
differing in digestibility and fermentability), as well as
proteins, to the GIT to address the issue. For example, the
dietary mix of carbohydrates might well be different to
ameliorate PWD than to maximize lean tissue gain.
5. Dietary crude protein in post-weaning diets
Another purported strategy to ameliorate PWD that is
perhaps more unambiguous is the alteration of the protein
quantity and (or) quality to manipulate gastrointestinal
structure and function, including that of the microbiota. An
imbalance between fermentable carbohydrates and potentially
fermentable protein (i.e. undigested nitrogen entering the
large intestine) has been proposed as a mitigating factor in the
aetiology of PWD of newly-weaned pigs (Bikker et al., 2006;
Piva et al., 2006; Kim et al., 2008). Metabolism of proteinaceous
materials by the microbiota in the large intestine may increase
levels of potentially toxic substances such as ammonia, amines,
indoles, phenols and branched-chain fatty acids (BCFA), which
have been implicated in the pathogenesis of PWD (Anderson et
al., 2000; Gaskins, 2001; Pluske et al., 2002; Houdijk et al.,
* P b 0.05, ** P b 0.01, *** P b 0.001, NS: not significant.
a
Adapted from McDonald et al. (2001a,b). Values represent treatment
means and standard error of means.
b
Rice: cooked white rice (702 g/kg, 4 g/kg dietary soluble NSP content)
plus animal protein sources (197 g/kg).
c
Barley: pearl barley (500 g/kg; 25 g/kg dietary soluble NSP content) plus
rice (275 g/kg) and animal protein sources (200 g/kg).
d
LW: live body weight.
e
Expressed as log10 CFU (colony-forming units) of haemolytic E. coli per
gram of mucosal scraping.
2007). Indeed, feeding weaned pigs a lower level of crude
protein caused lower ammonia concentrations in the small
intestine (Bikker et al., 2006) and decreased plasma urea
nitrogen, ammonia nitrogen and volatile fatty acids in the ileal
digesta (Nyachoti et al., 2006). These data are indicative of
reduced protein fermentation by the microbiota, and indicate
that feeding lower protein diets could be used to reduce PWD
in piglets fed antibiotic-free diets. A potential disadvantage of
feeding a low protein diet is compromised growth following
weaning caused by a reduced supply of essential AA, such as
isoleucine and valine (Nyachoti et al. 2006), however this can
be overcome by adding these amino acids in crystalline form.
Alternatively, the provision of additional fermentable carbohy-
drates in the diet of newly-weaned pigs can reduce the extent
or negative impact of protein fermentation, as has been shown
by Jeaurond et al. (2008).
A study by Heo et al. (2008) was conducted to test the
hypotheses that feeding a diet low in protein but supple-
mented with essential crystalline amino acids to maintain an
‘ideal pattern’ in the diet would first, reduce indices of protein
fermentation in the GIT and reduce the incidence of PWD, and
second, not compromise growth to approximately 15 weeks
of age. In this study the dietary protein level was reduced
from 243 g/kg to 173 g/kg while maintaining diet digestible
energy content, largely by replacing soybean meal with
wheat oat groats and barley. Reducing the dietary protein
decreased the levels of faecal ammonia nitrogen and PUN
indicative of decreased protein fermentation, which is
comparable to work published elsewhere (Nyachoti et al.,
2006). Commensurately, this strategy decreased the number
of antibiotic treatments, improved faecal consistency with an

Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
 C.F.M. de Lange et al. / Livestock Science xxx (2010) xxx–xxx
accompanying increase in the faecal DM content and did not
impact growth performance.
6. Plasma proteins and its alternatives
The addition of (spray-dried) plasma products to diets has
revolutionized the feeding of newly-weaned pigs, and
especially of pigs weaned before 18 days of age, in the last
15 years. Products such as spray-dried porcine plasma
(SDPP), where used, generally enhance performance through
increased feed intake and feed efficiency in the immediate
post-weaning period. Mechanisms for such effects have been
studied (see review by Lallès et al., 2004), including
immunoglobulin-independent, glycoprotein-enhanced pro-
tection against E. coli and the specific protection brought
about by plasma immunoglobulins (van Dijk et al., 2001).
Nevertheless, alternative products to SDPP have been studied
and in recent times, numerous experiments have examined
feeding bovine colostrum products to weanling pigs. This is
because bovine colostrum contains high levels of immuno-
globulins and growth factors such as IGF-1, and may be
viewed as a “safer” product to feed than animal plasma.
Dunshea et al. (2002) compared diets containing prepara-
tions of freeze-dried porcine plasma and freeze-dried bovine
colostrum after weaning at 14 days of age. These diets were
compared with a diet consisting of soybean meal and a diet
with animal protein sources. There were no effects of diet on
performance in the first 4 days after weaning. However,
between 18 and 21 days of age, pigs fed the soybean-meal-
containing diet ate less and grew slower than pigs fed the
other diets. By 35 days of age, pigs fed diets containing
colostrum and plasma were, on average, 6% heavier than pigs
fed the other diets. Under these experimental conditions the
use of bovine colostrum and a combination of animal protein
sources was comparable with using freeze-dried porcine
plasma in diets for early-weaned pigs. Inclusion of soybean
meal in diets, however, resulted in inferior performance. King
et al. (2007) and Boudry et al. (2008) noted improvements in
pig performance in the first 14 days after weaning at 21 days
of age with the inclusion of a bovine colostrum product in the
diet. King et al. (2007) also observed that villous height and
crypt depth were increased and decreased, respectively, in
the proximal jejunum, mid jejunum and distal ileum of pigs
consuming dietary bovine colostrum. Furthermore, mid-
jejunal lamina propria CD4(+) and CD8(+) T-lymphocyte
density was increased by 28 and 37%, respectively, in piglets
consuming dietary bovine colostrum. In another study, King
et al. (2008) evaluated the effects of dietary spray-dried
bovine and porcine plasma and spray-dried bovine colostrum
on growth performance and intestinal histology in weaner
pigs. No differences in average daily feed intake and growth
rate were observed among dietary treatment groups.
7. Selected feed additives
A large number of feed additives have been evaluated that
are aimed at either (1) enhancing the pigs' immune response
(e.g. immunoglobulin; ω-3 fatty acids, yeast derived ß-
glucans), (2) reducing pathogen load in the pig's gut (e.g.
organic and inorganic acids, high levels of zinc oxide, essential
oils, herbs and spices, some types of prebiotics, bacterio-
Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
5
phages, anti-microbial peptides), (3) stimulate establishment
of beneficial gut microbes (probiotics and some types of
prebiotics), and (4) stimulate digestive function (e.g. butyric
acid, gluconic acid, lactic acid, glutamine, threonine, cysteine,
and nucleotides). In this section general mechanisms and
recent developments are discussed for a select number of
feed additives.
7.1. Organic and inorganic acids
Various extensive reviews have been written about the
use of organic and inorganic acids in pig diets (e.g. Partanen,
2001; Decuypere and Dierick, 2003; Mroz et al., 2006). The
positive effects of feeding acids to pigs on gut health and
development, and indirectly on pig health and productivity,
may be attributed to various factors, including: (1) anti-
microbial activity of non-dissociated organic acids; (2)
lowering digesta pH, in particular in the stomach, aiding
protein digestion; (3) lowering stomach emptying rate; (4)
stimulating (pancreatic) enzyme production and activity in
the small intestine; and (5) providing nutrients that are
preferred by intestinal tissue thereby enhancing mucosal
integrity and function. Because of these beneficial and
synergistic effects, different combinations of organic and
inorganic acids are used widely in diets for newly-weaned
pigs, and used increasingly in diets for growing-finishing pigs
and sows. The effectiveness of feeding acids to pigs will vary
with the types and combinations of acid, the animal's state
and feed characteristics, in particular the diet's buffering
capacity (Blank et al., 1999; Mroz et al., 2006).
A relatively recent development is the encapsulation of
acids for targeted delivery to different gut segments. Studies,
such as those conducted by Piva et al. (2007) have shown that
relatively simple encapsulation is effective in delaying
absorption of dietary acids and allowing more effective
delivery of acids to the distal ileum, caecum and colon of
piglets. The latter may also be achieved by feeding acids in the
form of specific salts. For example, Canibe et al. (2001)
showed that feeding potassium-diformate is effective in
raising formic acid levels at the distal ileum of pigs at
28 days after weaning. The latter likely contributes to the
observed larger positive effects of feeding potassium-difor-
mate on growth performance of pigs, as compared to other
forms of formate (Overland et al., 2000). Decuypere and
Dierick (2003) stressed the strong anti-microbial properties
of medium-chain fatty acids. The combined feeding of
triacylglycerols containing medium-chain fatty acids and
exogenous lipolytic enzymes appears promising and requires
further exploring.
Among organic acids and in terms of impact on the
animal's physiology, lactic and butyric acid are of special
interest (e.g. Mroz et al., 2006). The beneficial effects of lactic
acid on pig growth performance have been documented and
may be attributed largely to its anti-microbial properties and
stimulation of endogenous enzyme production (see review
Mroz et al., 2006). Butyric acid is a preferred energy source for
enterocytes and has been shown to be effective in enhancing
intestinal cell proliferation (e.g. Sakata, 1987; Kien et al.,
2007). However, the beneficial effects of feeding butyric acid,
or relatively odorless sodium butyrate, on growth perfor-
mance of newly-weaned piglets have been small or could not
6 C.F.M. de Lange et al. / Livestock Science xxx (2010) xxx–xxx
be detected (Biagi et al., 2006; Weber and Kerr, 2008). This
lack of response may be attributed to endogenous fermenta-
tive butyric acid production (Sakata, 1987), which may be
stimulated by feeding easily fermentable fibre from sources
such as inulin or beet pulp to young pigs (Jeaurond et al.,
2008). Indeed, butyric acid-producing bacteria have been
identified in the mucosa-associated microbiota (Richards et
al., 2005). It is of interest to note that microbes can use
gluconic acid as substrate for butyric acid production.
Therefore, gluconic acid may be explored further as a rather
inexpensive source of butyric acid for use in animal nutrition
(Biagi et al., 2006).
A potential concern is the development of microbial
resistance to acids, which has been defined as the ability to
withstand an acid challenge of pH 2.5 or less (e.g. Castanie-
Cornet et al., 1999). Inducible and acid resistance proteins
have been observed in E. coli (Sato et al., 2000) and Salmonella
typhimurium (Bang et al., 2000). However, to our knowledge
no information is available about changes in the distribution
of genes involved in production of acid resistance proteins
across microbial populations in animals, in particular in
response to feeding organic acids.
7.2. Feed enzymes
The main goal for using exogenous feed enzymes in swine
diets has been to improve the nutritive value of feedstuffs.
This is achieved through several mechanisms including the
breakdown of anti-nutritional factors present in feed ingre-
dients, elimination of nutrient encapsulation effect thus
increasing availability, breakdown of specific chemical
bonds in raw materials that are otherwise not cleaved by
endogenous enzymes, thus releasing more nutrients, and
complementation of the enzymes produced by young animals
(Simon, 1998; Bedford and Schulze, 1998). Majority of the
vegetable feedstuffs used in swine diets contain a consider-
able amount of non-starch polysaccharides (NSP) whose anti-
nutritional effects are well-established and has been a subject
of intense research (de Lange et al., 2000). Thus, the use of
carbohydrase enzymes in swine diets has mainly focused on
eliminating the anti-nutritional activities associated with the
NSP components of feed. Indeed, several studies have shown
that with appropriate enzyme preparations, these anti-
nutritional effects can be minimized with a potential
improvement in the nutritional value of feedstuffs for
young pigs (Simons et al., 1990; Li et al., 1996; Omogbenigun
et al., 2004) and that a combination of different enzyme
activities is required for degradation of complex NSP to
improve nutrient utilization (Meng et al., 2005).
In addition to improved nutrient utilization, enzymes may
improve performance of young pigs through the production
of a variety of polysaccharide hydrolysis products that have a
direct effect on intestinal health by manipulating the growth
of gastrointestinal microorganisms (Vahjen et al., 1998;
Bedford, 2000; Williams et al., 2001; Pluske et al., 2002).
Indeed, studies with nursery pigs (Kim et al., 2003) and
broilers (Mathlouthi et al., 2002) suggest that the use of feed
enzymes may have a positive impact on intestinal health. In a
study with piglets, Inborr and Ogle (1988) reported that
supplementing moistened barley with a mixture of carbohy-
drate degrading enzymes was effective in reducing both the
Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
incidence and severity of diarrhoea. In recent studies utilizing
an in-situ model of secretory diarrhoea in piglets, Kiarie et al.
(2008) reported that NSP hydrolysis products generated by
incubating soybean meal and canola meal with a multi-
carbohydrase enzyme blend were beneficial in maintaining
intestinal barrier function during enterotoxigenic E. coli
infection. Similar observations were obtained with NSP
hydrolysis products from wheat and flaxseed. These observa-
tions could be explained by various mechanisms, including
the possibility that hydrolysis products interfere with the
attachment of pathogens to the intestinal mucosa, which is an
important first step in infection. These products may also act
as prebiotics (Cummings and MacFarlane, 2002), favouring
the proliferation of lactic acid-producing bacteria as has been
shown by Högberg and Lindberg (2004) and Kiarie et al.
(2007) and which in turn may indirectly prohibit the growth
of certain pathogenic species (Choi et al., 1994).
Feed enzymes may also improve gut health by reducing
the intestinal viscosity due to soluble NSP, which might
reduce rate of digesta passage, diffusion of digestive enzymes,
and increase endogenous gut protein secretions. This will in
turn increase substrate availability in the lower gut for
microbial proliferation (Verstegen and Williams, 2002;
Omogbenigun et al., 2004), as discussed in Section 6.
Among other effects, increased viscosity of intestinal digesta
in weaned pigs enhances proliferation of pathogenic bacteria
like enterotoxigenic E. coli and Brachyspira pilosicoli (McDo-
Donald et al., 2001a,b; Hopwood et al., 2002, 2004). Thus, it
has been hypothesized that supplementing swine diets with
enzymes to digest soluble NSP will minimize intestinal
microbial load which in turn will increase nutrient availability
to the host and minimize proliferation of pathogenic bacteria.
7.3. Pre and probiotics
A probiotic is defined as a live microorganism which when
administered in adequate amounts confers a health benefit
on the host (FAO/WHO 2002). For young piglets, a probiotic is
expected to deliver at least one of the following functions to
the GIT: (1) stimulating the development of a healthy
microbiota—predominated by beneficial bacteria, (2) pre-
venting enteric pathogens from colonization, (3) increasing
digestive capacity and lowering the pH, (4) improving
mucosal immunity, or (5) enhancing gut tissue maturation
and integrity. In practice, probiotic cultures need to have the
following characteristics in order to exert a positive effect on
pig performance: (1) the ability to colonize the GIT, (2) high
growth rate and a low requirement for nutrients, (3) suppress
enteric pathogens, either its cells or metabolites, (4) grown
easily on a large scale under commercial conditions; and (5)
survive in in-feed and from the manufacturing process with a
stable activity.
Lactic acid bacteria (LAB) (including Lactobacillus, Bifido-
bacterium, and Enterococcus) and bacilli have largely been
used as probiotic bacteria for food animal production in the
past. Lactobacillus, Bifidobacterium, and Enterococcus are
normal residents in the gut. Lactobacillus, in particular, is
dominant at the early stage of development of pig gut
microbiota (Richards et al., 2005), including the period
immediately post-weaning (Li et al., 2003). This group of
bacteria thus has an advantage over others in ecology for
 C.F.M. de Lange et al. / Livestock Science xxx (2010) xxx–xxx
colonizing the gut. LAB are acid producers through fermen-
tation, which can lower the pH of gut contents and benefit
intestinal functions. In addition, they can inhibit enteric
pathogens (Vandenbergh, 1993) and improve the host
immunity (Niers et al., 2005). Nonetheless, LAB are not
spore-forming bacteria and some of them are less tolerant to
oxygen. Survival during manufacturing and storage of feed, as
well as the delivery to the animal's GIT, could be a concern,
unless they are protected. In contrast to LAB, bacilli are Gram-
positive spore-forming bacteria; spores are relatively stable
during feed manufacturing and delivery. In general, Bacillus
species have a well-developed enzyme system. Some mem-
bers have been used for commercial production of enzymes,
such as amylases and proteases (Schallmey et al., 2004),
which may complement the pig's endogenous digestive
enzymes. In general, probiotic effects are associated with
specific bacterial isolates. How to select and maintain the
property of a probiotic, therefore, remains critical and
challenging in the successful development and application
of probiotics.
There have been a large number of in vivo studies to assess
the effect of probiotics on the performance of newly-weaned
piglets. Recently, it was reported that in 30 out of 31
performance studies, piglets demonstrated a positive growth
response to the supplement of a combination of Bacillus
lichiniformis and Baccillus subtilis in diets (Kremer, 2006).
Different LAB isolates, mainly from Lactobacillus and Bifido-
bacterium species, have also been reported to have positive
effects on the performance of newly-weaned piglets
(reviewed by Stein and Kil, 2006). In particular, Lactobacillus
sobrius 001T with an inhibitory effect towards enterotoxi-
genic E. coli (ETEC) K88 was recently demonstrated to have a
probiotic effect by reducing ileal ETEC abundance and
promoting the growth of piglets orally challenged with
ETEC K88 (Konstantinov, 2005). However, there are also
reports of in vivo studies showing no responses of piglets to
tested probiotic bacteria (Jost and Bracher, 1999). Further-
more, an adverse effect of the supplement with Lactobacillus
rhamnosus GG (originally used for human subjects) has even
been described, in which the supplement enhanced ETEC
excretion in faeces and reduced the growth of weaning
piglets orally challenged with an ETEC (reviewed by Lallès
et al., 2007).
The inconsistency in the reports of probiotic effects
indicates the high degree of complexity in the development
and application of probiotics. It highlights the need for
scientific research to better understand the mode of action
and molecular mechanisms underlying the probiotic effects.
Also, scientific evaluation of newly-developed probiotic
products and good quality control practices at every step
throughout the manufacturing, maintenance, handling and
application are critical to ensure the achievement of expected
probiotic effects. Clearly, easy measurement(s) of the char-
acteristics relating to probiotic effects would assist such
quality control, and this is often lacking. Probiotic bacteria are
live organisms with dynamic changes in their metabolism.
Phenotypes of a particular probiotic are subject to the
influence by many internal and external factors, which will
affect the efficacy of probiotics. Identification of relationships
among these factors is thus required for effective use and
development of novel probiotics.
Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
7
A prebiotic is a non-digestible food ingredient that alters
the composition, or metabolism, of the gut microbiota in a
beneficial manner. It is, therefore, expected that prebiotics
benefit the host in a manner similar to probiotics. In practice,
bifidobacteria and lactobacilli have been almost exclusively
the targets of prebiotics (Bouhnik et al., 2004). For newly-
weaned piglets, the dietary supplement of fermentable
carbohydrates is generally regarded as a comparatively
straightforward approach to improve microbiota composition
and functionality of both the small and large intestine
(Williams et al., 2001; Bauer et al., 2006). Recent studies
demonstrated that the addition of sugarbeet pulp, inulin,
lactulose and wheat starch to the diet, designed to stimulate
the fermentation along the entire gut, altered the composi-
tion of bacterial microbiota in the gut of newly-weaned
piglets (Konstantinov et al., 2003, 2004). The supplement of
inulin to different basal diets also affected the proportion of
piglets with detectable levels of bifidobacteria, but not
lactobacilli (Loh et al., 2006). Inulin has also been shown to
be able to improve small intestinal architecture when dietary
lactose levels were low (Pierce et al., 2006). Thus increased
intake of prebiotics can contribute to the gut health.
Prebiotics are generally cheaper, lower risk, and easier to
handle and to incorporate into diets than probiotics.
Combining prebiotics with probiotics (symbiotics) may
increase the efficacy of probiotic effects on gut health and
development in newly-weaned piglets.
7.4. Essential oils
Essential oils are volatile components of plants that have
been used in food preparation since antiquity. These oils are
generally recognized as safe (GRAS) by the Food and Drug
Administration (FDA) of the United States and have been
used as artificial flavourings and preservatives, in the
manufacture of perfume, and in over-the-counter formula-
tions of medicines. Some essential oils have strong anti-
microbial activity (Kalemba and Kunicka, 2003), particularly
those containing phenolic structures (Dorman and Deans,
2000). The strong anti-microbial activity of phenolic essential
oils, such as carvacrol and thymol, is attributed to their
delocalized electrons and the presence of a hydroxyl group on
the phenolic ring (Ultee et al., 2002). The oils initiate damage
to the bacterial cell membrane, which compromises pH
homeostasis and equilibrium of inorganic ions across the
bacterial cell membrane (Lambert et al., 2001). This leads to
the collapse of the proton motive force and depletion of the
ATP pool in the microbe (Ultee et al., 2002). Essential oils
have also been shown to have a certain degree of selectivity.
Lin et al. (2000) reported more inhibition towards Gram-
negative Salmonella and E. coli than to Gram-positive Listeria
monocytogenes. In our in vitro studies, we also observed that
essential oils exhibited a high efficacy against pure cultures of
S. Typhimirium DT104, E. coli O157:H7, and E. coli K88 with
little inhibition towards Lactobacillus and Bifidobacterium in
mediums that contained pig cecal digesta (Si et al., 2006a).
Essential oils usually have the characteristic odour or flavour
of the plant from which it is extracted. Therefore, they may
improve performance of animals not only by controlling
enteric pathogens but also by increasing palatability of diets.
8 C.F.M. de Lange et al. / Livestock Science xxx (2010) xxx–xxx
Essential oils have been extensively studied and used
in a wide range of food systems to increase the safety and
shelf life of foods (Burt, 2004). However, their impacts on
growth performance of newly-weaned pigs have been
inconsistent, although changes in gut microbiota compo-
sition were observed (Manzanilla et al., 2004; Gong et al.,
2008). The anti-microbial activity of essential oils tends to
be diminished when they are tested in vivo (Gößling,
2001). Essential oils are generally hydrophobic. They can
be absorbed quickly after oral, pulmonary or dermal
administration (Kohlert et al., 2000). In piglets, essential
oils were found to be absorbed nearly completely in the
stomach and the proximal small intestine within 2 h after
oral administration (Michiels et al., 2008). We also found
that feed contributes to the loss of anti-microbial activity
of essential oils in pig performance studies (Si et al.,
2006b); oils were mostly absorbed to feed articles as
revealed by gas chromatography (unpublished data).
Together, these observations suggest that essential oils
need protection for delivery to the target site within the
pig's GIT to exert their anti-microbial activity. As men-
tioned earlier in the section about organic and inorganic
acids, microencapsulation may be a means to achieve this.
In fact, human clinical studies have shown that enteric-
coated essential oil (peppermint) capsules exhibited a
better performance in treatment of irritable bowel syn-
drome compared to the uncoated formulation (Liu et al.,
1997; Logan and Beaulne, 2002). The improvements have
presumably been attributed to the delayed absorption of
the coated peppermint oils and the prolonged contact
between peppermint oil and bacterial cells. In our recent
effort, carvacrol was used as a model essential oil and
successfully encapsulated in microcapsules made from Ca-
alginate hydrogel using an emulsion-extrusion technology
with high encapsulation efficiency. Encapsulated carvacrol
retained its high anti-microbial activity towards E. coli K88
in a culture medium, as well as in a simulated gastroin-
testinal model (Wang et al., 2009). It remains to be
determined if the encapsulated essential oil will reduce
the burden of enteric pathogens in the gut of weaning
piglets and improve pig performance.
8. Conclusions
Large amounts of research have been conducted evaluat-
ing the impact of a wide range of feed ingredients and feed
additives on various aspects of gut health and development in
pigs, in order to improve growth performance around the
time of weaning while minimizing the use of antibiotics and
rather expensive feed ingredients, such as milk products. A
better understanding of the mechanisms whereby nutrients,
feed ingredients and feed additives influence animal physi-
ology will lead to the development of alternatives to in-feed
antibiotics. Given the considerable advances made in the
understanding of intestinal nutrient utilization and metabo-
lism, a complimentary goal in nutrition might be to formulate
young pig diets with the specific task of optimizing the
growth, function and health of the gut. A large number of feed
additives have been evaluated that are aimed at (1)
enhancing the pig's immune response, (2) reducing pathogen
load in the pig's gut, (3) stimulate establishment of beneficial
Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117
gut microbes, and (4) stimulate digestive function. In this
review, a select number of feed additives (organic and
inorganic acids, feed enzymes, pre- and probiotics, essential
oils) are discussed. These additives all have the potential to
improve pig productivity. However, more research is required
to optimize the pigs' response to these feed additives under
varying conditions. A key concern with several of these
additives is their effective delivery to the targeted location in
the pig's gastrointestinal tract. A combination of different
approaches may provide the most effective alternative to in-
feed antibiotics.
Conflict of interest
All authors acknowledge that there that are no conflicts of
interest concerning the information that is provided in the
paper.
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Please cite this article as: de Lange, C.F.M., et al., Strategic use of feed ingredients and feed additives to stimulate gut health
and development in young pigs, Livestock Science (2010), doi:10.1016/j.livsci.2010.06.117